Ponesimod

Overview

Ponesimod, sold under the brand name Ponvory, is a medication for the treatment of multiple sclerosis. It is a sphingosine-1-phosphate receptor modulator.[1][2] WP

The most common side effects include upper respiratory tract infection, hepatic transaminase elevation, and hypertension.[1][2][3] WP

Ponesimod was approved for medical use in the United States in March 2021, and in the European Union in June 2021.[1][2][3] WP

Uses, dosage and effects

Medical uses

Ponesimod is indicated for the treatment of relapsing forms of multiple sclerosis including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.[1][3] WP

Risks and side effects

Adverse effects

Common adverse effects in studies were temporary bradycardia (slow heartbeat), usually at the beginning of the treatment, dyspnoea (breathing difficulties), and increased liver enzymes (without symptoms). No significant increase of infections was observed under ponesimod therapy. QT prolongation is detectable but was considered to be too low to be of clinical importance in a study.[4][5] WP

Pharmacology

Mechanism of action

Like fingolimod, which is already approved for the treatment of multiple sclerosis, ponesimod blocks the sphingosine-1-phosphate receptor. This mechanism prevents lymphocytes (a type of white blood cells) from leaving lymph nodes. Ponesimod is selective for subtype 1 of this receptor, S1P₁.[4][6] WP

History

Clinical trials

In a 2009–2011 Phase II clinical trial including 464 multiple sclerosis patients, ponesimod treatment resulted in fewer new active brain lesions than placebo, measured during the course of 24 weeks.[4][7] WP

In a 2010–2012 Phase II clinical trial including 326 patients with psoriasis, 46 or 48% of patients (depending on dosage) had a reduction of at least 75% Psoriasis Area and Severity Index (PASI) score compared to placebo in 16 weeks. The approval is already applied for in 2020.[4][8][9] WP⚠ A word may be missing here. It reads this way in the source too.

In a 2015–2019 Phase III randomised, double-blind clinical trial of 1133 adult patients with relapsing multiple sclerosis, those under ponesimod treatment showed a 30% reduction in annual relapse rate and a significantly reduced number of new inflammatory lesions on brain MRI by 56% compared to those taking teriflunomide.[10] WP

In October 2020, Janseen-Cilag International NV submitted an application for the modification of agreed pediatric investigation plan (PIP) to European Medicines Agency (including deferral and waiver criteria). This application was launched for the amendments of proposed changes against the European Medicines Agency’s decisions issued in November 2012 and April 2018. The approved procedure has already started in December 2022. To evaluate pharmacodynamics and pharmacokinetics efficacy of ponesimod in pediatric patients with relapsing-remitting multiple sclerosis (RRMS); a multicenter, randomized, double blind clinical study of duration of 108 weeks treatment for age group 10 to less than 18 years, is in progress. The clinical trial will end in November 2027.[11][12] WP

Legal status

Legal status

In March 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Ponvory, intended for the treatment of active relapsing forms of multiple sclerosis. The applicant for this medicinal product is Janssen-Cilag International N.V. Ponesimod was approved for medical use in the European Union in May 2021.[3][13] WP

Chemistry

Formula

C23H25ClN2O4S PC

CAS number

854107-55-4 PC

Molar mass (g/mol)

461.0 PC

IUPAC name (computed by PubChem)

(5Z)-5-[[3-chloro-4-[(2R)-2,3-dihydroxypropoxy]phenyl]methylidene]-3-(2-methylphenyl)-2-propylimino-1,3-thiazolidin-4-one PC

SMILES

CCCN=C1N(C(=O)/C(=C/C2=CC(=C(C=C2)OC[C@@H](CO)O)Cl)/S1)C3=CC=CC=C3C PC

InChIKey

LPAUOXUZGSBGDU-ULCCENQXSA-N PC

PubChem CID

11363176

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Ponvory- ponesimod tablet, film coated Ponvory- ponesimod kit
2. Other Janssen Announces U.S. FDA Approval of Ponvory (ponesimod), an Oral Treatment for Adults with Relapsing Multiple Sclerosis Proven Superior to Aubagio (teriflunomide) in Reducing Annual Relapses and Brain Lesions. 19 March 2021
3. Journal / agency Ponvory EPAR. 24 March 2021
4. Journal / agency Spreitzer H. Neue Wirkstoffe – Ponesimod. Österreichische Apothekerzeitung. 29 September 2014
5. Journal / agency Hoch M, Darpo B, Brossard P, Zhou M, Stoltz R, Dingemanse J. Effect of ponesimod, a selective S1P1 receptor modulator, on the QT interval in healthy individuals. Basic & Clinical Pharmacology & Toxicology. May 2015. doi:10.1111/bcpt.12336 · PMID 25287214
6. Other Ponesimod
7. Journal / agency Olsson T, Boster A, Fernández Ó, Freedman MS, Pozzilli C, Bach D, Berkani O, Mueller MS, Sidorenko T, Radue EW, Melanson M. Oral ponesimod in relapsing-remitting multiple sclerosis: a randomised phase II trial. Journal of Neurology, Neurosurgery, and Psychiatry. November 2014. doi:10.1136/jnnp-2013-307282 · PMID 24659797 · PMC4215282
8. Journal / agency Vaclavkova A, Chimenti S, Arenberger P, Holló P, Sator PG, Burcklen M, Stefani M, D'Ambrosio D. Oral ponesimod in patients with chronic plaque psoriasis: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet. December 2014. doi:10.1016/S0140-6736(14)60803-5 · PMID 25127208
9. Other Ozanimod bei schubförmiger MS zugelassen. 6 July 2020
10. Other Europe Approves Ponvory Ponesimod for Multiple Sclerosis
11. Journal / agency EMA. EMEA-000798-PIP01-09-M03. 17 September 2018
12. Journal / agency Rose K, Müller T. Children with multiple sclerosis should not become therapeutic hostages. Therapeutic Advances in Neurological Disorders. September 2016. doi:10.1177/1756285616656592 · PMID 27582894 · PMC4994785
13. Journal / agency Ponvory: Pending EC decision. 25 March 2021

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.